Prostaglandins (PGs) mimic most effects of thyrotropin (TSH) on thyroid. In addition, inhibition of TSH effect by PG antagonists and our observation that TSH increases PG levels in thyroid suggest that intrathyroidal PGs may modulate responsivity to TSH and, perhaps, to abnormal stimulators (e.g., long-acting thyroid stimulator (LATS) and LATS-Protector). Ongoing studies in this area may yield further insight into regulation of thyroid function in health and disease. The role of LATS in the pathogenesis of Graves' hyperthyroidism is increasingly uncertain; the pathogenetic role of LATS-Protector and other thyroid-stimulating IgGs in this disorder is now under active study. The enzyme Ornithine Decarboxylase (ODC) catalyzes the initial step in polyamine synthesis. We have shown that, in thyroid, ODC activity may serve as a biological marker for the growth-promoting effects of TSH. The role of this enzyme in normal and abnormal thyroid growth and function is currently under study. Investigation of TSH and prolactin (PRL) dynamics in euthyroid and hyperthyroid Graves' disease suggests disorder hypothalamic-pituitary function may represent yet another facet of this disorder. Studies of hypothalamic-pituitary function in Graves' patients using thyrotropin-releasing hormone (TRH) and gonadotropin-releasing hormone (GnRH,LH-RH) now represent a major clinical research objective in our laboratory. Ongoing studies suggest that thyroidal response to TSH may be inhibited by its own hormones and that this represents a short-loop negative feedback mechanism regulating thyroid function. Fluorescent thyroid scanning provides an in-vivo index of endogenous iodine content. We are using this approach to determine whether thyroidal iodine content in untreated and treated hyperthyroidism correlates with response to antithyroid drug therapy and/or restoration of suppressibility.